• Immune response of COVID-19 patients see dramatic changes on a day-to-day basis, especially in the early stage of the illness
• Immune responses between individual COVID-19 patients can be significantly different
• Findings show the importance of closely studying disease progression and immune responses when developing therapeutics or vaccines Singapore, 4 April 2020
– Scientists from the SingHealth Duke-NUS Academic Medical Centre (AMC) have found that Coronavirus Disease 2019 (COVID-19) patients show a dynamic and fluctuating immune response, particularly in the early stages of the disease. The findings, published in the journal Cell Host & Microbe, highlight the importance of closely studying COVID-19’s progression and immune responses in patients when developing therapeutics or vaccines.
Immune response is how the human body recognises and fights against viruses, bacteria or substances that appear foreign or harmful. In studying COVID-19 and how the immune system responds to it, a team of clinicians and scientists from the Viral Research and Experimental Medicine Centre (ViREMiCS) at the SingHealth Duke-NUS AMC, analysed the blood and gene expression profiles of three hospitalised COVID-19 patients daily.
They found dramatic gene expression changes in the patients as the disease progressed. There was a highly dynamic expression of pro-inflammatory genes (genes that promote inflammation) and a significant variation in the patients’ immune responses from one day to another, especially in the early stage of the illness. For example, a patient’s expression of certain pro-inflammatory genes could have a sudden drastic peak, and this would correlate with the period when the patient became more sick and experienced respiratory distress, such as breathlessness.
“On the research front, we found that it is critical to track COVID-19 patients’ immune responses closely since they can change drastically over the course of the disease. A one-time ‘snapshot’ of their genetic response may not be accurate for the complete understanding of COVID-19 and the development of therapeutics and vaccines. On the clinical front, we hope that understanding these immune changes can eventually help doctors pre-empt them so that the right therapy can be administered at the right time,” said senior author of the study, Associate Professor Jenny Low, Co-Director of ViREMiCS, Senior Consultant, Department of Infectious Diseases, Singapore General Hospital, and Associate Professor at the Emerging Infectious Diseases (EID) programme, Duke-NUS Medical School (Duke-NUS).
“These findings will help all of us in the scientific community ensure that our understanding of COVID-19 is robust, even as we continue to learn more about the virus every day,” said Dr Eugenia Ong, Senior Research Fellow at ViREMiCS, and the Duke-NUS EID programme, who is first author of the study.
The study also suggested that interleukin-1, known to be pro-inflammatory, and its related pathways, as well as T-cells, a type of cell that helps fight viral infections in the body, could play an important role in COVID-19. The team is continuing their research with more COVID-19 patients to further validate these findings.
Leveraging the same research method used in this study, the ViREMiCS team is partnering with industry in speed-testing and evaluating potential COVID-19 vaccines and therapeutics. “In evaluating vaccines, we want to see how well the vaccines do against the early gene signature changes of the patients. The closer these gene signature changes resemble the actual disease, the closer we are to finding a potentially effective vaccine,” said Dr Ong.
Reference: Ong EZ, Chan YFZ, Leong WY, Lee NMY, Kalimuddin S, Mohideen SMH, Chan KS, Tan AT, Bertoletti A, Ooi EE and Low JGH (2020). A dynamic immune response shapes COVID-19 progression. Cell Host & Microbe. DOI: 10.1016/j.chom.2020.03.021